www.perpetualcommotion.com
"Give with a free hand, but give only your own."
 -- J.R.R. Tolkien The Children of Hurin
- Curcumin -

Lots of good info about curcumin here:
Margaret's Corner: MY DISCOVERY OF CURCUMIN
http://margaret.healthblogs.org/life-with-myeloma/discovery-of-curcumin/
[Look for the many links to the related pages about curcumin in the column
on right hand side of her page, under the "pages" heading.]

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Curcumin (Turmeric extract, diferuloylmethane)
     - is a major active component of the food flavoring turmeric (Curcuma longa)

See also Curcumin, Copper, Vitamin D

[Need more info-- Read in Reader's Digest-- villages in India where there is a low incidence of AD.  Could be a genetic thing, like the villages in Italy where heart disease is rare.]

Some observations on the spectrum of dementia
Neurology India, Year: 2004 Volume: 52  Issue: 2  Page: 213-214
Sanjeev Jha, R Patel
Department of Neurology, SGPGIMS, Lucknow, India

A study was designed to generate epidemiological and clinical data on dementia, in a teaching hospital in India. It was conducted on 124 (94 male and 30 female) elderly patients (aged more than 60 years) presenting with clinical syndrome of dementia (DSM-3). Their age range was 64-78 (mean 65.7 4.1) years. Detailed clinical, biochemical, radiological and electrophysiological evaluation was done to establish etiology. Patients with psychiatric ailments, cranial trauma and tumors were excluded. The study period was 4.2 years. Multi-infarct dementia (MID) was observed to be commonest cause of dementia and was present in 59 (47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB) and neurocysticercosis (NCC). Alcohol-related dementia was present in 13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in 9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria) in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob Disease. We conclude that AD, which is irreversible and common in the west, is relatively uncommon in India as compared to MID, infections and malnutrition, which are potentially treatable.
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2004;volume=52;issue=2;spage=213;epage=214;aulast=Jha

A report in the Journal of Biological Chemistry, February 18, 2005 uses the phrase "disaggregated" amyloid-β fibrils.  Does this mean it disolved amyloid-β?

From Wikipedia:  Little curcumin is absorbed.  Co-supplementation with 20mg piperine (extract of black pepper, a.k.a. Bioperine) increased absorption by 2000%.  However, peperine can interfere with the metabolism of other drugs, and should be taken with caution, if at all.  I'm leaning toward not using peperine.

Curcumin is also a potent iron and copper chelator.

In a study using mice, low-dose curcumin was found to enhance adult hippocampal neurogenesis.
See, Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus.  High dose levels were found to be "cytotoxic": "Curcumin exerted biphasic effects on cultured NPC - low concentrations stimulated cell proliferation, whereas high concentrations were cytotoxic."
http://www.ncbi.nlm.nih.gov/pubmed/18362141?dopt=Abstract

There are anectdotal reports that 500mg of curcumin twice per day will "normalize" high blood pressure.  Those who are on blood pressure medications for high blood pressure should be aware of the possibility of overmedication should this effect of curcumin develop.

Effect on TNF-Alpha:

I know that curcumin is used as an anti-inflammatory agent, so I searched Google on curcumin and TNF. I found research papers saying that curcumin inhibited TNF, and some that said that it "sensitized" cancer cells to TNF (which I guess is a good thing). Here's an example:

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-3YVDRW0-6P&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7a734d2000776a9f4ca641b1bd4aae02

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Feline Lymphoma
Back in May of this year (2010), our little 16 year old Siamese kitty started having trouble breathing.  It was quite apparent that whatever her problem was, it was in her nose.  After a couple of expensive trips to the vet and a specialist, a biopsy of a mass in her sinus cavity above the soft palate was positive for T-cell lymphoma.  We immediately started giving her the steroid prednisolone.  I also remembered reading that curcumin was being investigated for combating human cancers.  A quick check of the Internet revealed that it is also being investigated for treating feline cancers.  We started giving our kitty 500mg of Jarrow brand curcumin (turmeric extract) divided into three doses.  At the point we started all of this, she wasn't eating.  All we could do is get her to drink a few teaspoons of Wiskas' kitty milk.  It took a while, but her appetite has returned.  She's gained back all the weight she lost, and then some.  We don't know how long it will last, but as of this date, August 22, 2010, she's doing fine.  Since we didn't even expect her to make it to July 4, this has indeed been a pleasant surprise. We also don't know if her apparent remission is due to the curcumin, the steroid, or a combination of both.  I think it is the latter.

Here is some more info on feline lymphoma...

Lymphoma in Cats
http://www.veterinarypartner.com/Content.plx?P=A&A=1446

Curcumin for Cats
http://margaret.healthblogs.org/2007/10/11/curcumin-for-cats/

Intestinal Cancer and Curcumin for Dogs
http://www.dogcancerblog.com/intestinal-cancer-and-curcumin-for-dogs/

Spice derivative could prove useful in feline cancer therapy
http://veterinarynews.dvm360.com/dvm/Feline+Center/Spice-derivative-could-prove-useful-in-feline-canc/ArticleStandard/Article/detail/622362

Status update:  October 9, 2010 The cat is still doing fine.  She seems to be healthier than she has for the past couple of years.  She has gained weight.  She used to have coughing spells.  That's pretty much stopped.  Also, she had been throwing up quite often for the past several years.  She hasn't been doing this since the lymphoma symptoms subsided.

Status update:  December 10, 2010 The cat is still doing fine.  We took her off of the steroid prednisolone for a while.  She started having "coughing" fits again, and threw up a couple of times.  Since we put her back on it, this cleared up.  We're still giving her 500mg of curcumin in her food, divided in three parts throughout the day.

Status update:  February 26, 2011
The cat is still doing fine on the prednisolone & curcumin regimen.  She still has a fast heartbeat and probably poor kidney function, but the lymphoma still has not returned.  If she makes it to May, it will have been 1 year since diagnosis.  If I remember correctly, treating feline lymphoma with steroids (like prednisolone) alone, expected survival time is only several weeks.  If she makes it to July, she will be 17.  That's a ripe old age for a Saimese.

Status update:  March 26, 2011 We took the cat to the vet today because she hasn't been eating as much as she should.  The vet thinks that her kidney function has gotten worse.  Don't know what to do about that.  However, there isn't any obvious sign of a return of the lymphoma.  We'll get results of blood work next week.

Status update:  April 9, 2011 The test results from the vet are that her kidney function is not worse than it was a year ago, but not good.  No obvious sign of lymphoma returning, so we are treating her for renal falure.  Standard therapy is injections of 100ml of saline solution once a week.  This seems to really perk her up and she starts eating again.  So, as far as the curcumin goes, I think it is a success.  Now I need to find out what to do to help with the kidney function.

Status update:  August 1, 2011 Still going.  Kidney problems are getting worse, but still managable.  We have to give her fluid injections (~150ml under the skin) every week.  We've cut back on both the prednisolone curcumin.  Prednisolone every other day, and about 250mg of curcumin in her food per day. From what I've read, we should only have expected 6 to 8 months with using prednisolone alone.  Combination
chemotherapies are expected to give maybe 20 months.  So, even if this works as well as those much more expensive options, we will be doing good.

Last Update:  The kitty passed away May 19, 2012 of age-related kidney failure.  She was 17 years, 10 months old.  Pure-bred siamese cats typically live to 14. The vet told us,"Some kitties just try to outlive their kidneys".  The curcumin and prednisolone kept her with us for two years past the diagnosis of lymphoma. There was no sign of a relapse. We stopped the curcumin and prednisolone in the fall of 2011.

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Multiple Myeloma

http://margaret.healthblogs.org/life-with-myeloma/discovery-of-curcumin/my-curcumin-protocol/


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HSV-1 (Herpes Simplex Virus, Cold Sore Virus)

Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity.
Virology. 2008 Apr 10;373(2):239-47. Epub 2008 Jan 14.
Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ.

Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Abstract

Curcumin, a phenolic compound from the curry spice turmeric, exhibits a wide range of activities in eukaryotic cells, including antiviral effects that are at present incompletely characterized. Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression. Entry of viral DNA to the host cell nucleus and binding of VP16 to IE gene promoters was not affected by curcumin, but recruitment of RNA polymerase II to those promoters was significantly diminished. However, these effects were observed using lower curcumin concentrations than those required to substantially inhibit global H3 acetylation. No changes were observed in histone H3 occupancy or acetylation at viral IE gene promoters. Furthermore, p300 and CBP recruitment to IE gene promoters was not affected by the presence of curcumin. Finally, disruption of p300 expression using a short hairpin RNA did not affect viral IE gene expression. These results suggest that curcumin affects VP16-mediated recruitment of RNA polymerase II to IE gene promoters by a mechanism independent of p300/CBP histone acetyltransferase activity.

PMID: 18191976 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/18191976
Free full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668156/?tool=pubmed


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Brain Injury/Stroke

Compound Derived from Curry Spice Is Neuroprotective Against Stroke and Traumatic Brain Injury

ScienceDaily (Dec. 15, 2010) — A synthetic derivative of the curry spice turmeric, made by scientists at the Salk Institute for Biological Studies, dramatically improves the behavioral and molecular deficits seen in animal models of ischemic stroke and traumatic brain injury (TBI)... One compound, called CNB-001, which was derived from curcumin, the active ingredient in the spice turmeric, proved highly neuroprotective in all of the assays; it also enhanced memory in normal animals...
http://www.sciencedaily.com/releases/2010/12/101215092254.htm


New Hybrid Drug, Derived from Common Spice, May Protect, Rebuild Brain Cells After Stroke
Released: 2/8/2011 8:00 AM EST
Source: Cedars-Sinai Medical Center
....The scientists created a new molecule from curcumin, a chemical component of the golden-colored spice turmeric, and found in laboratory experiments that it affects mechanisms that protect and help regenerate brain cells after stroke. Research scientist Paul A. Lapchak, Ph.D., director of Translational Research in the Department of Neurology at Cedars-Sinai Medical Center, [presented] these findings at the American Heart Association International Stroke Conference in Los Angeles on Wednesday, Feb. 9... The new curcumin-hybrid compound—CNB-001—does not attack clots but instead repairs stroke damage at the molecular level that feed and support the all-important brain cells, neurons...
http://www.newswise.com/articles/view/573199/

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References:

Turmeric-Based Drug Effective On Alzheimer Flies
ScienceDaily (Feb. 14, 2012) — Curcumin, a substance extracted from turmeric, prolongs life and enhances activity of fruit flies with a nervous disorder similar to Alzheimers, according to new research. The study conducted at Linköping University, indicates that it is the initial stages of fibril formation and fragments of the amyloid fibrils that are most toxic to neurons...
http://www.sciencedaily.com/releases/2012/02/120214100554.htm

Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila.
Ina Caesar, Maria Jonson, K. Peter R. Nilsson, Stefan Thor, Per Hammarström
PLoS ONE, 2012; 7 (2): e31424 DOI: 10.1371/journal.pone.0031424
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0031424

Scientists ID possible biomarker to gauge Alzheimer's prognosis, effect of therapies
University of California - Los Angeles
17-Mar-2011
...They incubated the immune cells overnight with amyloid beta to test the cells' ability to "turn on" MGAT3. They also added a synthetic form of curcumin to some of the cells to gauge the effect it had on MGAT3 expression and the absorption of amyloid beta.

Based on the results, the researchers identified three groups of Alzheimer's patients.

Type 0 patients: This group had very low expression of MGAT3 and very low absorption rates of amyloid beta.

Type I patients: This group also had low expression of MGAT3 and low amyloid beta absorption rates, but the strength of the MGAT3 message and the absorption of amyloid beta increased when researchers stimulated the macrophages with synthetic curcumin.

Type II patients: This group initially had high amyloid beta absorption rates, but when scientists added synthetic curcumin, MGAT3 expression lessened and absorption was reduced.

In addition, researchers found that for Type I and Type II patients, the clearing of amyloid beta was dependent on vitamin D3, a type of vitamin D that occurs naturally in these cells. When they blocked vitamin D3 use by the macrophages in the laboratory, they found that absorption of amyloid beta suffered.

"These findings demonstrate three very different levels of immunity and possible reactions to natural therapies of vitamin D3 and curcumin," Fiala said. "These differences could point to a new way to track the progression of Alzheimer's disease and the effectiveness of these natural therapies based on an individual patient's immunity."

Fourteen of the 20 Alzheimer's disease patients have been followed for two years, and researchers noted that those who were Type 0 had a worse two-year prognosis regarding the loss of their ability to live independently than the other two types of patients... During the study, researchers also noted that one Type II patient who underwent hip surgery experienced temporary cognitive dysfunction related to the general surgery anesthesia, which is a phenomenon that can occur. Researchers checked the patient's MGAT3 immunity and found that the patient's ability to clear amyloid beta had declined after surgery but improved in later months, along with cognitive function, possibly due to the vitamin D3 supplementation the patient had undertaken...
http://www.eurekalert.org/pub_releases/2011-03/uoc--sip031711.php

Common Yellow Lab Dye Profoundly Extends Lifespan in Healthy Nematodes, and Slows Alzheimer's Disease-Like Pathology in Worms
ScienceDaily (Mar. 30, 2011) — Basic Yellow 1, a dye used in neuroscience laboratories around the world to detect damaged protein in Alzheimer's disease, is a wonder drug for nematode worms. In a study appearing in Nature, the dye, also known as Thioflavin T (ThT)... Alavez said curcumin, the active ingredient in the popular Indian spice turmeric, also had a significant positive impact on both healthy worms and those bred to express a gene associated with Alzheimer's. "People have been making claims about the health benefits of curcumin for many years. Maybe slowing aging is part of its mechanism of action,"...
http://www.sciencedaily.com/releases/2011/03/110330131258.htm

Reference: Silvestre Alavez, Maithili C. Vantipalli, David J. S. Zucker, Ida M. Klang, Gordon J. Lithgow. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature, 2011


Evaluation of local drug-delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: A clinical and microbiological study.
J Indian Soc Periodontol. 2011 Jan;15(1):35-8.
Behal R, Mali AM, Gilda SS, Paradkar AR.
SourceDepartment of Periodontology, Bharati Vidyapeeth Dental College and Hospital, Pune, Maharashtra, India.

Abstract

AIM: To compare the effect of experimental local-drug delivery system containing 2% whole turmeric (gel form) as an adjunct to scaling and root planing (SRP) with the effect achieved using SRP alone by assessing their respective effects on plaque, gingival inflammation, bleeding on probing pocket depth, relative attachment levels and trypsin-like enzyme activity of "red complex" microorganisms, namely, Bacteroides forsythus, Porphvromonas gingivalis and Treponema denticola.

MATERIAL AND METHODS: Thirty subjects with chronic localized or generalized periodontitis with pocket depth of 5 to 7 mm were selected in a split-mouth study design. Control sites received SRP alone, while experimental sites received SRP plus experimental material (2% whole turmeric gel). Plaque index (PI), gingival index (GI), sulcus bleeding index (SBI), probing pocket depth (PPD), relative attachment loss (RAL), microbiological study of collected plaque sample for trypsin-like activity of "red complex" by BAPNA assay were the parameters recorded on day 0, 30 days and 45 days.

RESULTS: Both groups demonstrated statistically significant reduction in PI, GI, SBI, PPD; and gain in RAL. Significant reduction in the trypsin-like enzyme activity of "red complex" (BAPNA values) was observed for both the groups when compared to the baseline activity. Greater reduction was seen in all the parameters in the experimental group in comparison to the control group.

CONCLUSION: The experimental local drug-delivery system containing 2% whole turmeric gel can be effectively used as an adjunct to scaling and root planing and is more effective than scaling and root planing alone in the treatment of periodontal pockets.
PMID:21772719[PubMed - in process] PMCID: PMC3134044
http://www.ncbi.nlm.nih.gov/pubmed/21772719
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134044/?tool=pubmed


Curcumin Info (Curcumin (diferuloylmethane) is a major active component of the food flavoring turmeric (Curcuma longa))
Cancer Adjuvant Therapy
- Also mentions curcumin inhibiting TNF-alpha
http://www.lef.org/protocols/prtcl-027c.shtml

Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells.

PMID: 9764849 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/9764849
http://www.nature.com/jid/journal/v111/n4/full/5600153a.html

Curcumin for skin cancer...
http://robertrister.com/supplements-curcumin/curcumin-for-skin-cancer/


[ Embrel inhibits TNF-alpha.  Some who have the Tobonick “Perispinal Embrel Injection” procedure respond favorably to it. Does curcumin do the same thing as Embrel to some degree???]

Tumor necrosis factor-alpha (TNF-alpha): Researchers at the University of Kentucky showed that TNF-alpha acts as a catalyst in cytokine production, stimulating interleukin-6 (IL-6) and -8 (IL-8) and activating NF-kB (Blanchard et al. 2001). Curcumin inhibits TNF-alpha, thus blocking TNF-alpha, NF-kB pathways, and the emergence of pro-inflammatory cytokines (Xu et al. 1997-1998; Li et al. 2001; Literat et al. 2001). To read more about proinflammatory cytokines, turn to the protocol Cancer: Gene Therapies, Stem Cells, Telomeres and Cytokines.
http://www.lef.org/protocols/prtcl-027c.shtml

Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells.
Xu YX, Pindolia KR, Janakiraman N, Chapman RA, Gautam SC.
Hematopathol Mol Hematol. 1997-1998;11(1):49-62.
Source: Division of Hematology/Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.
Abstract
We have previously demonstrated that anti-inflammatory and antioxidant compound curcumin (diferuloyl-methane) inhibits the expression of monocyte chemoattractant protein-1 (MCP-1/JE) in bone marrow stromal cells by suppressing the transcriptional activity of the MCP-1/JE gene. Since both AP-1 (TRE) and NF-kB (kB) binding motifs are present in the promoter of MCP-1/JE gene, we examined the effect of curcumin on IL1 alpha- and TNF-alpha-induced activation of ubiquitous transcription factors AP-1 and NF-kB by electrophoretic mobility shift assay and Western blotting. IL1 alpha and TNF-alpha rapidly induced both AP-1 and NF-kB DNA binding activities in +/+(-)1.LDA11 stromal cells. However, treatment of these cells with curcumin blocked the activation of AP-1 and NF-kB by both cytokines. These data suggest that inhibition of MCP-1/JE transcription by curcumin involves blocking of AP-1 and NF-kB activation by IL1 alpha or TNF-alpha.
PMID: 9439980 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/9439980


Curcumin reduces α-synuclein induced cytotoxicity in Parkinson's disease cell model
Min S Wang1,2, Shanta Boddapati1, Sharareh Emadi1 and Michael R Sierks1*
* Corresponding author: Michael R Sierks sierks@asu.edu
Author Affiliations
1 Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006 USA
2 Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364 USA
BMC Neuroscience 2010, 11:57 doi:10.1186/1471-2202-11-57
http://www.biomedcentral.com/1471-2202/11/57

Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model.
Wang MS, Boddapati S, Emadi S, Sierks MR.
BMC Neurosci. 2010 Apr 30;11:57.
Source: Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA.
Abstract
BACKGROUND:

Overexpression and abnormal accumulation of aggregated alpha-synuclein (alphaS) have been linked to Parkinson's disease (PD) and other synucleinopathies. alphaS can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase alphaS aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models.

RESULTS:

Here we show that curcumin can alleviate alphaS-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of alphaS and extracellular addition of oligomeric alphaS increase ROS which induces apoptosis, suggesting that aggregated alphaS may induce similar toxic effects whether it is generated intra- or extracellulary.

CONCLUSIONS:

Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders.
PMID: 20433710 [PubMed] PMCID: PMC2879277
http://www.ncbi.nlm.nih.gov/pubmed/20433710
Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879277/?tool=pubmed
            http://www.biomedcentral.com/content/pdf/1471-2202-11-57.pdf


Curcumin
Definitions:  Free Dictionary
              Wikipedia
"Curcumin is the principal curcuminoid of the Indian curry spice turmeric. The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in solution"

"Curcumin is known for its antitumor, antioxidant, anti-amyloid and anti-inflammatory properties. Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis."

Curcumin Inhibits Formation of Amyloid {beta} Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo
J. Biol. Chem., Vol. 280, Issue 7, 5892-5901, February 18, 2005

"Alzheimer's disease (AD) involves amyloid {beta} (A{beta}) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential A{beta} binding, we investigated whether its efficacy in AD models could be explained by effects on A{beta} aggregation... When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small {beta}-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates A{beta} as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD."
http://www.jbc.org/cgi/content/full/280/7/5892

A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease
UCLA Dept. of Neurology, Alzheimer’s Disease Research Center

"There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer’s disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1702408
also http://www.ingentaconnect.com/content/ben/car/2005/00000002/00000002/art00006?token=004b19a063c1a9a3d332b25757d5c4f6d4e227a677e442f20675d3b7646255c23796d7a3144

An Indian Spice for Alzheimer's?

"Researchers here in the United States have been pursuing clues to the effects of curcumin, a compound found in the spice turmeric that is responsible for the yellow color of Indian curry and American mustard. Studies show that elderly villagers in India appear to have the lowest rate of Alzheimer's disease in the world. Researchers speculate that curcumin, which has powerful antioxidant and anti-inflammatory properties might play a role, because Indians eat turmeric with almost every meal."
http://www.drweil.com/drw/u/id/QAA72328

Curcumin, the Curry Spice
Part 2

"The levels of beta-amyloid in AD mice that were given low doses of curcumin were decreased by around 40% in comparison to those AD mice that were not treated with curcumin. In addition, low doses of curcumin also caused a 43% decrease in the so-called "plaque burden" that these beta-amyloids have on the brains of AD mice. Surprisingly, those AD mice that received high doses of curcumin did not show any decreases in beta-amyloid levels or plaque burden in comparison with untreated mice. While the exact reason for this finding is not yet clear, the results of it are intriguing: low doses of curcumin were actually more effective than high doses in combating the neurodegenerative process of AD."
http://www.stanford.edu/group/hopes/treatmts/curcumin/ai2.html

Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro.

"Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro..."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14994335

Spice Protects Brain Cells, Could Prevent Alzheimer's Disease

"In their study, researchers exposed rat brain cells to various concentrations of curcumin, then analyzed the cells 24 hours later. Indeed, they found HO-1 as well as two other protective enzymes. However, higher concentrations of curcumin caused substantial cell damage -- with no increase in the protective HO-1 protein, she reports."
http://www.webmd.com/alzheimers/news/20040419/hot-tip-curry-may-protect-aging-brain

The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse
The Journal of Neuroscience, November 1, 2001, 21(21):8370-8377

"To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta , a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta -amyloid (Abeta ), soluble Abeta , and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease."
http://www.jneurosci.org/cgi/content/abstract/21/21/8370

Curcumin helps clear Alzheimer's plaques
Oct. 4 (UPI)

"Curcumin improved ingestion of amyloid beta by immune cells in 50 percent of patients with Alzheimer's disease," said Fiala.
http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20061004-125430-3088r

UCLA/VA Study Finds Chemical Found in Curry May Help Immune System Clear Amyloid Plaques Found in Alzheimer’s Disease
Date: October 3, 2006

"UCLA/VA researchers found that curcumin — a chemical found in curry and turmeric — may help the immune system clear the brain of amyloid beta, which form the plaques found in Alzheimer's disease. Published in the Oct. 9 issue of the Journal of Alzheimer's Disease, the early laboratory findings may lead to a new approach in treating Alzheimer's disease by enhancing the natural function of the immune system using curcumin, known for its anti-inflammatory and anti-oxidant properties."
http://newsroom.ucla.edu/page.asp?RelNum=7366
also, http://www.hbri.org/NewsandEvents_PR_10-3-06.htm

Molecular Orbital Basis for Yellow Curry Spice Curcumin's Prevention of Alzheimer's Disease

"It is demonstrated by using high-level ab initio computations that the yellow curcumin pigment, bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, in the east Indian root plant turmeric (Curcuma longa) exhibits unique charge and bonding characteristics that facilitate penetration into the blood-brain barrier and binding to amyloid-β (Aβ). Alzheimer's disease is caused by Aβ accumulation in the brain cells combined with oxidative stress and inflammation. Consistent with the recent experimental work by Cole and co-workers (Yang, F., et al. J. Biol. Chem. 2004, 280, 5892-5901) that demonstrates curcumin pigment's binding ability to Aβ both in vivo and in vitro, it is shown here that curcumin possesses suitable charge and bonding features to facilitate the binding to Aβ."
http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i10/abs/jf0603533.html

Spice Up Your Brain
Preserve brain function with spicy foods.
By PsychologyToday.com

"About a tablespoon of curry a day, or 200 mg of curcumin, does the trick, says Dr. Sally Frautschy, associate professor of medicine at UCLA. “I eat curry at least 4 times a week,” she reports."

"Other spices are thought to possibly contain medicinal properties. Ginger and cinnamon are getting a close look. A powerful antioxidant in ginger called zingerone appears so far to have brain-protective properties like curcumin. Cinnamon may also have effects in the brain."
http://health.msn.com/centers/alzheimers/articlepage.aspx?cp-documentid=100126581&wa=wsignin1.0



Curcuminoids as potential new iron-chelating agents: spectroscopic, polarographic and potentiometric study on their Fe(III) complexing ability

Authors: Borsari M.; Ferrari E.; Grandi R.; Saladini M.1
Source: Inorganica Chimica Acta, Volume 328, Number 1, 30 January 2002 , pp. 61-68(8)

Marco Borsari, Erika Ferrari, Romano Grandi and Monica Saladini
Department of Chemistry, University of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy
 
Abstract

"The pKa values of curcumin and diacetylcurcumin are, here doubtless, determined by means of spectroscopic and potentiometric measurements, and the enolic proton is the more acidic one. The interaction of Fe3+ with curcumin and diacetylcurcumin, in water/methanol 1:1 solution, leads to the formation of the complex species [FeH2CU(OH)2] and [FeDCU(OH)2] (H2CU and DCU=curcumin or diacetylcurcumin monoanion, respectively) which prevails near pH 7. At more basic condition the prevailing species are [FeH2CU(OH)3]− and [FeDCU(OH)3]−, which prevent metal hydroxide precipitation. 1H NMR data state that the dissociated β-diketo moiety of the ligands is involved in metal chelation. The pKa value of the deprotonation reaction is strongly anticipated by the metal ion, as shown by UV spectral data. The stability constants, evaluated from potentiometric data, are near to that of desferrioxamine, which is, by now, the only iron-chelating agent for clinical use...Curcumin and diacetylcurcumin coordinate Fe(III) through β-diketone moiety, form stable complexes. The prevailing species at physiological pH is [FeH2CU(OH)2] whose stability constant is near to those of iron-sequestering agents for clinical use."
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TG5-44W31SJ-8&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ec04b29401cf941169efb08fb8bb3f70

Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models.
J Alzheimers Dis. 2004 Aug;6(4):367-77; discussion 443-9.
Baum L, Ng A.

Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin. lwbaum@cuhk.edu.hk

"Curcumin is a polyphenolic diketone from turmeric. Because of its anti-oxidant and anti-inflammatory effects, it was tested in animal models of Alzheimer's disease, reducing levels of amyloid and oxidized proteins and preventing cognitive deficits. An alternative mechanism of these effects is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Metals can induce Abeta aggregation and toxicity, and are concentrated in AD brain. Chelators desferrioxamine and clioquinol have exhibited anti-AD effects. Using spectrophotometry, we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+ showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at least two curcumin molecules. The interaction of curcumin with copper reached half-maximum at approximately 3-12 microM copper and exhibited positive cooperativity, with Kd1 approximately 10-60 microM and Kd2 approximately 1.3 microM (for binding of the first and second curcumin molecules, respectively). Curcumin-iron interaction reached half-maximum at approximately 2.5-5 microM iron and exhibited negative cooperativity, with Kd1 approximately 0.5-1.6 microM and Kd2 approximately 50-100 microM. Curcumin and its metabolites can attain these levels in vivo, suggesting physiological relevance. Since curcumin more readily binds the redox-active metals iron and copper than redox-inactive zinc, curcumin might exert a net protective effect against Abeta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB."

PMID: 15345806 [PubMed]
http://iospress.metapress.com/content/yy1rf8ctbf08lulu/

Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus.
Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, Chung HY, Mattson MP, Lee J.
Pharmacy, Pusan National University, Busan 609-735.

"Curcumin is a natural phenolic component of yellow curry spice, which is used in some cultures for the treatment of diseases associated with oxidative stress and inflammation. Curcumin has been reported capable of preventing the death of neurons in animal models of neurodegenerative disorders, but its possible effects on developmental and adult neuroplasticity are unknown. In the present study, we investigated the effects of curcumin on mouse multi-potent neural progenitor cells (NPC) and adult hippocampal neurogenesis. Curcumin exerted biphasic effects on cultured NPC - low concentrations stimulated cell proliferation, whereas high concentrations were cytotoxic. Curcumin activated extracellular signal regulated kinases (ERKs) and p38 kinases, cellular signal transduction pathways known to be involved in the regulation of neuronal plasticity and stress responses. Inhibitors of ERKs and p38 kinases effectively blocked the mitogenic effect of curcumin in NPC. Administration of curcumin to adult mice resulted in a significant increase in the number of newly-generated cells in the dentate gyrus of hippocampus, indicating that curcumin enhances adult hippocampal neurogenesis. Our findings suggest that curcumin can stimulate developmental and adult hippocampal neurogenesis, a biological activity that may enhance neural plasticity and repair."

PMID: 18362141 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/18362141?dopt=Abstract

Vitamin D, Curcumin May Help Clear Amyloid Plaques Found In Alzheimer's Disease
ScienceDaily (July 15, 2009)
"UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer's disease. The early research findings, which appear in the July issue of the Journal of Alzheimer's Disease, may lead to new approaches in preventing and treating Alzheimer's by utilizing the property of vitamin D3 — a form of vitamin D — both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta..."
http://www.sciencedaily.com/releases/2009/07/090715131558.htm

Curry spice helps pre-diabetes
31st July 2012
Researchers in Thailand say that patients with type 2 diabetes could benefit from taking supplements containing a compound found in curry spice.

Curcumin, a compound in the spice turmeric, may help prevent diabetes in people who have pre-diabetes, according to the research, which was published in the journal Diabetes Care.
http://www.healthcare-today.co.uk/news/curry-spice-helps-pre-diabetes/22447/

[ NEED link to Diabetes Care journal article ]

An Overview of Curcumin in Neurological Disorders
S. K. Kulkarni* and A. Dhir1
Indian J Pharm Sci. 2010 Mar-Apr; 72(2): 149–154.
doi:  10.4103/0250-474X.65012
PMCID: PMC2929771

Abstract
Curcumin, the principal curcuminoid found in spice turmeric, has recently been studied for its active role in the treatment of various central nervous system disorders. Curcumin demonstrates neuroprotective action in Alzheimer's disease, tardive dyskinesia, major depression, epilepsy, and other related neurodegenerative and neuropsychiatric disorders. The mechanism of its neuroprotective action is not completely understood. However, it has been hypothesized to act majorly through its anti-inflammatory and antioxidant properties. Also, it is a potent inhibitor of reactive astrocyte expression and thus prevents cell death. Curcumin also modulates various neurotransmitter levels in the brain. The present review attempts to discuss some of the potential protective role of curcumin in animal models of major depression, tardive dyskinesia and diabetic neuropathy. These studies call for well planned clinical studies on curcumin for its potential use in neurological disorders.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929771/


Multiple antidepressant potential modes of action of curcumin: A review of its antiinflammatory, antioxidant, mmune-modulating and neuroprotective effects
Adrian L Lopresti1, Sean D Hood [2], Peter D Drummond [1]
1 School of Psychology, Murdoch University, Perth, Western Australia, 6150, Australia
2 School of Psychiatry & Clinical Neurosciences, University of Western Australia,
Perth, Western Australia, 6009, Australia
http://researchrepository.murdoch.edu.au/12507/1/Curcumin_as_a_potential_treatment_for_major_depression.pdf

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